It is the purpose of this research to study the arrangement of phospholipids in cellular membranes and to elucidate the mechanism of action of hormones at the membrane level. The plasma membrane from rat liver, human erythrocytes, human adipocytes and rat adipocytes will serve as the source for these membranes. The arrangement of phospholipids in the membrane will be examined by use of penetrating and non-penetrating chemical probes such as flourodinitrobenzene and trinitrobenzene sulfonic acid and cross-linking agents such as difluorodinitrobenzene and suberimidate. The nature of hormone binding (insulin and epinephrine) to the membranes will be studied and attempts will be made to see if and how the hormone ending is altered in abnormal states such as diabetes, obesity, hypothyroidism and hyperthyroidism. It is hoped to elucidate the biochemical mechanism whereby thyroxine regulates the epinephrine response in fat cells. The mechanism of coupling of the hormone receptor with adenylate cyclase activation or inhibition will constitute a longer term project. Attempts to isolate and purify the hormone receptor in the membrane will be postponed since it will require more staff and money than the grant can support.